The major general objective of the Specialized Center of Research in Hypertension is to provide new knowledge that will contribute to improved diagnosis, treatment and possible prevention of hypertension. The Center at Vanderbilt is a multidisciplinary research group that includes investigators in Biochemistry, Clinical Pharmacology, Endocrinology, Vascular Surgery, Urology, Radiology and Biostatistics. The relative effectiveness of pharmacologic therapy, renal artery bypass and translumenal dilatation in renovascular hypertension will be investigated. The cardiac and renal consequences of various methods of treatment will be assessed. Carotid artery stenosis is a frequent ancillary complication and patients with hypertension, and the value of surgical correction of a symptomatic carotid artery stenosis will be assessed. The molecular and cellular mechanisms controlling the secretion of renin will be investigated. The secretion and activation of prorenin will be studied using cloned and cultured juxtoglomerular cells. The molecular mechanism of prorenin activation will be investigated. Utilizing highly purified human renin, a radioimmunoassay for human renin is under development. Evidence for a protein that binds renin in plasma has been obtained and this substance will be further purified and its possible function evaluated. The physiological role of prostaglandin I2 in mediating renin release will be investigated in experimental animal models, in normal humans and in patients with disease states known to be associated with altered levels of plasma renin activity. Factors that affect trophic hormone stimulation and suppression of mineralocorticord production by the adrenal gland will be investigated. An exaggerated renin response to volume depletion in borderline hypertension will be further studied and its mechanism sought. Several studies will address the pharmacology of the sympathetic nervous system, including the mechanism of action of methyldopa, the clinical pharmacology of prazosin, improved biochemical methods for early detection of pheochromacytoma and an investigation of the regulation of beta-adrenergic receptors in man.